New Publication from Dr. Cheryl Arrowsmith and Dr. Mathieu Lupien

MBP scientists Dr. Cheryl Arrowsmith and Dr. Mathieu Lupien have co-authored a new Nature article entitled ‘PRMT inhibition induces a viral mimicry response in triple-negative breast cancer’.

MBP researchers Dr. Daniel de Carvalho and Dr. Benjamin Haibe-Kains also contributed to the paper, alongside several other collaborators.

Article Abstract
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.